Tsoumakidou lab published a new study in the Journal of Experimental Medicine on the role of fibroblasts in peripheral adaptive immunity against lung cancer
A new study published in the Journal of Experimental Medicine by Tsoumakidou lab shows how and why immunological hot spots in lung tumors are sustained by cancer antigen presenting fibroblasts.
A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found in breast and pancreatic tumors and are considered to be immunosuppressive. In a new study published in the Journal of Experimental Medicine, entitled “Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts”, Tsoumakiodu Lab shows that antigen-presenting fibroblasts are frequent in human lung non-small cell carcinomas, where they seem to actively promote rather than suppress MHCII immunity. Lung apCAFs directly activated the TCRs of effector CD4 T cells and at the same time produced C1q, which acted on T cell C1qbp to rescue them from apoptosis. Fibroblast-specific MHCII or C1q deletion impaired CD4 T cell immunity and accelerated tumor growth, while inducing C1qbp in adoptively transferred CD4 T cells expanded their numbers and reduced tumors. Collectively, Tsoumakidou Lab characterized in the lungs a subset of antigen-presenting fibroblasts with tumor-suppressive properties and suggests that cancer immunotherapies might be strongly dependent on in situ MHCII antigen presentation.
Dimitra Kerdidani, Emmanouil Aerakis, Kleio-Maria Verrou, Ilias Angelidis, Katerina Douka, Maria-Anna Manio, Petros Stamoulis, Katerina Goudevenou, Alejandro Prados, Christos Tzaferis, Vasileios Ntafis, Ioannis Vamvakaris, Evangelos Kaniaris, Konstantinos Vachlas, Evangelos Sepsas, Anastasios Koutsopoulos, Konstantinos Potaris, Maria Tsoumakidou. Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts. J Exp Med . 2022 Feb 7;219(2):e20210815. doi: 10.1084/jem.20210815. Epub 2022 Jan 14.
[Pubmed]